POS0578 CORRELATION BETWEEN EXPRESSION LEVELS OF MIR-155 AND MIR-223 IN SYNOVIAL FLUID AND ULTRASOUND SCORES FOR ACTIVE SYNOVITIS IN RHEUMATOID ARTHRITIS PATIENTS
Authors: R. Shumnalieva, D. Kachakova, R. Kaneva, Z. Kolarov, S. Monov
Journal: Annals of the Rheumatic Diseases (2021)

Background: MicroRNAs (miRNAs) are a class of small, non-coding RNAs that negatively regulate gene expression at posttranscriptional level. In rheumatoid arthritis studies have shown that miRNA are differentially expressed systemically as well as locally in the inflamed joints [1,2]. The correlation between their systemic or local expression levels and scores for disease activity and progression in RA make them possible candidate for biomarkers in the clinical practice. Objectives: To analyze the expression levels of miR-155 and miR-223 in synovial fluid (SF) from RA patients in regard to the ultrasound scores for disease activity. Methods: A total number of 48 RA patients according to the 1987 ACR criteria were included in the study. Expression levels of miR-155 and miR-223 SF were determined by qPCR (SybrGreen technology) and compared to healthy controls (HCs). Relative changes of gene expression levels of the studied miRNAs were calculated by 2 -ΔΔCt method. Musculoskeletal ultrasound (MSUS) examination was performed by two independent examiners on ESAOTE, MyLab60 using both grey scale and power Doppler technic. A semi-quantitative assessment of the peripheral joints was performed for detecting joint inflammation and determining the grade of synovial thickening and the degree of vascularization. Ultrasound features for active disease were correlated to the local expression of the studied miRNAs. SPSS was used for statistical analysis. Results: RA SF showed overexpression of miR-155 (in 79.17%, p=1.63x10 -4 ) and of miR-223 (in 79.17%, p=1.64x10 -3 ) when compared to HCs and both miRNAs could be used to differentiate RA patients from HCs (р=8.0х10 -5 and р=2.8х10 -4 , respectively). When we analyzed the correlation between the diagnosis, the expression of miRNAs and the changes on the musculoskeletal ultrasound examination we found a statistically significant correlation between the presence of synovitis and the degree of the power Doppler signal on MSUS and the local expression of miR-223 (p=6.19 x 10 -4 and p=0.003, respectively). SF levels of miR-223 correlated also with the degree of synovial hypertrophy on MSUS (p=0.013). The results for miRNA-155 were not statistically significant. Conclusion: The correlation between the local expression of miR-223 and the ultrasound features of active joint inflammation shows that this miRNA might be a better candidate for local disease biomarker than miR-155. Further analysis with larger sets is needed to confirm if altered local miRNA expression could be used in the clinical practice as biomarker for disease activity especially in cases with subclinical synovitis. References: [1]Filková M, Aradi B, Šenolt L, et al. Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis. ARD, 2014; 73: 1898-1904. [2]Kriegsmann, M., Randau, T.M., Gravius, S. et al. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis. Virchows Arch, 2016; 469, 93–100. Acknowledgements: The study was supported by Grant 14-D/2012 and Grant 60/2013 funded by Medical University-Sofia. Disclosure of Interests: Russka Shumnalieva: None declared, Darina Kachakova: None declared, Radka Kaneva: None declared, Zlatimir Kolarov Speakers bureau: Amgen, Pfizer, Novartis, Abbvie, Roche, Astra-Zeneka, Simeon Monov Speakers bureau: Amgen, Pfizer, Novartis, Abbvie, Roche, Astra-Zeneka